This invention relates to a process for the preparation of crystalline loracarbef monohydrate.
The .beta.-lactam antibiotic of the formula (I) ##STR2## is the potent orally active antibiotic known as loracarbef. The antibiotic is described, for example, by Hashimoto et al. in U.S. Pat. No. 4,335,211, issued Jun. 15, 1982.
The above compound comes in various forms, including the crystalline monohydrate form, which is disclosed in European Patent Publication 0,311,366 having a publication date of Apr. 12, 1989. Other known solvate forms of the compound are disclosed in Eckrich et al. U.S. Pat. No. 4,977,257. The crystalline dihydrate form of loracarbef is disclosed in European Patent Publication 0,369,686 having a publication date of May 23, 1990. As indicated in the EPO application, the crystalline monohydrate may be prepared by first suspending the dihydrate in water and effecting solution by the addition of acid followed by the adjustment of the pH with base, or by the addition of base followed by acid.
It has been determined that loracarbef crystalline monohydrate is a fine "hair-like" crystal which results in very slow filtration. In filtering the monohydrate, the crystals tend to from a mat on the filter medium which prevents or reduces the ability to complete filtration, such that the crystals must be washed with water. As loracarbef monohydrate is moderately soluble in water, (approximately 10 mg/ml), loss of yield results when such washes are needed.
What is needed in light of the above difficulties is a process for preparing crystalline loracarbef monohydrate in a more efficient manner, that is, to avoid the requirement of filtering the crystalline monohydrate.